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Effect of Curcumol on NOD-Like Receptor Thermoprotein Domain 3 Inflammasomes in Liver Fibrosis of Mice

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Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To investigate the effect of curcumol on NOD-like receptor thermoprotein domain 3 (NLRP3) inflammasomes, and analyze the mechanism underlying curcumol against liver fibrosis.

Methods

Thirty Kunming mice were divided into a control group, a model group and a curcumol group according to a random number table, 10 mice in each group. Mice were intraperitoneally injected with 40% carbon tetrachloride (CCl4:peanut oil, 2:3 preparation) at 5 mL/kg for 6 weeks, twice a week, for developing a liver fibrosis model. The mice in the control group were given the same amount of peanut oil twice a week for 6 weeks. The mice in the curcumol group were given curcumol (30 mL/kg) intragastrically, and the mice in the model and control groups were given the same amount of normal saline once a day for 6 weeks. Changes in liver structure were observed by hematoxylin and eosin (HE) and Masson staining. Liver function, liver fiber indices, and the expression of interleukin (IL)-10 and tumor necrosis factor-α (TNF-α) levels were determined by automatic biochemical analyzer and enzyme linked immunosorbent assay kit. Immunoblotting and reverse transcription-quantitative PCR (RT-qPCR) were performed to detect the expression of NLRP3 inflammasome-related molecules, TGF-β and collagen.

Results

HE and Masson staining results showed that the hepatocytes of the model group were arranged irregularly with pseudo-lobular structure and a large amount of collagen deposition. The mice in the curcumol group had a significant decrease in liver function and liver fibers indices compared with the model group (P<0.05); RT-qPCR and Western blotting results reveal that, in the curcumol group, the mRNA and protein expression levels of NLRP3, IL-1 β, Caspase 1 and gasdermin D decreased significantly compared with the model group (P<0.05); immunohistochemical results showed that in the curcumol group, the protein expression levels of NLRP3 and IL-1 β decreased significantly compared with the model group (P<0.05).

Conclusion

A potential anti-liver fibrosis mechanism of curcumol may be associated with the inhibition of NLRP3 inflammasomes and decreasing the downstream inflammatory response.

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References

  1. Tacke F, Trautwein C. Mechanisms of liver fibrosis resolution. J Hepatol 2015;63:1038–1039.

    Article  Google Scholar 

  2. Ellis EL, Mann DA. Clinical evidence for the regression of liver fibrosis. J Hepatol 2012;56:1171–1180.

    Article  Google Scholar 

  3. Wree A, Eguchi A, McGeough MD, Pena CA, Johnson CD, Canbay A, et al. NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice. Hepatology 2014;59:898–910.

    Article  CAS  Google Scholar 

  4. Gross O, Thomas CJ, Guarda G, Tschopp J. The inflammasome: an integrated view. Immunol Rev 2011;243:136–151.

    Article  CAS  Google Scholar 

  5. Szabo G, Csak T. Inflammasomes in liver diseases. J Hepatol 2012;57:642–654.

    Article  CAS  Google Scholar 

  6. Meng N, Xia M, Lu YQ, Wang M, Boini KM, Li PL, et al. Activation of NLRP3 inflammasomes in mouse hepatic stellate cells during Schistosoma J. infection. Oncotarget 2016;7:39316–39331.

    Article  Google Scholar 

  7. Kayagaki N, Stowe IB, Lee BL, O’Rourke K, Anderson K, Warming S, et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 2015;526:666–671.

    Article  CAS  Google Scholar 

  8. Zheng Y, Wang JH, Liang TJ, Wang L, Zhao TJ. Effect of curcumol on Rho-ROCK signaling pathway in hepatic stellate cells. Chin Hosp Pharm J (Chin) 2019;39:1517–1520.

    Google Scholar 

  9. Xu JM, Xu SY, Zhang YF. Establishment of a mouse liver fibrosis model induced by carbon tetrachloride. Chin Pharm Bull (Chin) 2000;16:339–341.

    CAS  Google Scholar 

  10. Zheng Y, Wang JR, Liu LL, Wang JH, Zhao TJ. Molecular mechanism of the anti-liver fibrosis effect of curcumol: an analysis based on the TLR4/NF-κB signaling pathway. J Clin Hepatol (Chin) 2020;36:1508–1513.

    CAS  Google Scholar 

  11. Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005;115:209–218.

    Article  CAS  Google Scholar 

  12. Poilil Surendran S, George Thomas R, Moon MJ, Jeong YY. Nanoparticles for the treatment of liver fibrosis. Int J Nanomed 2017;12:6997–7006.

    Article  Google Scholar 

  13. Mona H, Ismail MP. Reversal of liver fibrosis. Saudi J Gastroenterol 2009;15:72–79.

    Article  Google Scholar 

  14. Ouyang X, Ghani A, Mehal WZ. Inflammasome biology in fibrogenesis. Biochim Biophys Acta 2013;1832:979–988.

    Article  CAS  Google Scholar 

  15. Watanabe A, Sohail MA, Gomes DA, Hashmi A, Nagata J, Sutterwala FS, et al. Inflammasome-mediated regulation of hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol 2009;296:G1248–G1257.

    Article  CAS  Google Scholar 

  16. Krenkel O, Tacke F. Liver macrophages in tissue homeostasis and disease. Nat Rev Immunol 2017;17:306–321.

    Article  CAS  Google Scholar 

  17. Awad F, Assrawi E, Jumeau C, Georgin-Lavialle S, Cobret L, Duquesnoy P, et al. Impact of human monocyte and macrophage polarization on NLR expression and NLRP3 inflammasome activation. PLoS One 2017;12:e0175336.

    Article  Google Scholar 

  18. Weiskirchen R, Tacke F. Cellular and molecular functions of hepatic stellate cells in inflammatory responses and liver immunology. Hepatobiliary Surg Nutr 2014;3:344–363.

    PubMed  PubMed Central  Google Scholar 

  19. Gieling RG, Wallace K, Han YP. Interleukin-1 participates in the progression from liver injury to fibrosis. Am J Physiol Gastrointest Liver Physiol 2009;296:G1324–G1331.

    Article  CAS  Google Scholar 

  20. Kamari Y, Shaish A, Vax E, Shemesh S, Kandel-Kfir M, Arbel Y, et al. Lack of interleukin-1alpha or interleukin-1beta inhibits transformation of steatosis to steatohepatitis and liver fibrosis in hypercholesterolemic mice. J Hepatol 2011;55:1086–1094.

    Article  CAS  Google Scholar 

  21. Snouwaert JN, Nguyen M, Repenning PW, Dye R, Livingston EW, Kovarova M, et al. An NLRP3 mutation causes arthropathy and osteoporosis in humanized mice. Cell Rep 2016;17:3077–3088.

    Article  CAS  Google Scholar 

  22. Robert S, Gicquel T, Victoni T, Valença S, Barreto E, Bailly-Maître B, et al. Involvement of matrix metalloproteinases (MMPs) and inflammasome pathway in molecular mechanisms of fibrosis. Biosci Rep 2016;36:e00360.

    Article  Google Scholar 

  23. Dong HY, Li Y, Zhao GM. Comparative observation of serum liver fibrosis indexes and liver pathology. Intern J Epidemiol Infect Dis (Chin) 2006;2:81–82.

    Google Scholar 

  24. Li Q, Ou XJ, Li J, Jia JD, Wang BE. A comparative study of serum liver fibrosis indexes and liver pathology. J Clin Hepatol (Chin) 2004;3:155–156.

    Google Scholar 

  25. Kew MC. Serum aminotransferase concentration as evidence of hepatocellular damage. Lancet 2000;355:591–592.

    Article  CAS  Google Scholar 

  26. Chen CJ, Yang HI, Su J. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006;295:65–73.

    Article  CAS  Google Scholar 

  27. Iloeje UH, Yang HI, Su J. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology 2006;130:678–686.

    Article  Google Scholar 

  28. Peiro C, Lorenzo O, Carraro R, Sanchez-Ferrer CF. IL-1 β inhibition in cardiovascular complications associated to diabetes mellitus. Front Pharmacol 2017;8:363.

    Article  Google Scholar 

  29. Altamirano-Barrera A, Barranco-Fragoso B, Méndez-Sánchez N. Management strategies for liver fibrosis. Ann Hepatol 2017;16:48–56.

    Article  CAS  Google Scholar 

  30. Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG, Wu H, et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature 2016;535:153–158.

    Article  CAS  Google Scholar 

  31. Liu Y, Zhang T, Zhou Y, Li J, Liang X, Zhou N, et al. Visualization of perforin/gasdermin/complement-formed pores in real cell membranes using atomic force microscopy. Cell Mol Immunol 2019;16:611–620.

    Article  CAS  Google Scholar 

  32. Sagoo P, Garcia Z, Breart B, Lemaitre F, Michonneau D, Albert ML, et al. In vivo imaging of inflammasome activation reveals a subcapsular macrophage burst response that mobilizes innate and adaptive immunity. Nat Med 2016;22:64–71.

    Article  CAS  Google Scholar 

  33. Karki R, Kanneganti TD. Diverging inflammasome signals in tumorigenesis and potential targeting. Nat Rev Cancer 2019;19:197–214.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Guangxi University of Chinese Medicine for providing the laboratory equipment and technological support.

Author information

Authors and Affiliations

  1. Department of Medicine, Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine, Nanning, 530021, China

    Yang Zheng, Lei Wang & Jia-hui Wang

  2. Department of Teaching, the First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530022, China

    Lu-lu Liu

  3. Department of Physiology, College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, 530021, China

    Tie-jian Zhao

Authors
  1. Yang Zheng
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  2. Lei Wang
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  3. Jia-hui Wang
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  4. Lu-lu Liu
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Contributions

Zheng Y and Zhao TJ designed this experiment. Zheng Y and Wang L performed the molecular biology detection and wrote this article; Liu LL and Wang JH were responsible for the pathology detection; Zheng Y and Zhao TJ revised this article. And all authors agreed the final version for publication.

Corresponding author

Correspondence to Tie-jian Zhao.

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Conflict of Interest

The authors declare that there are no financial conflicts of interest.

Supported by the National Natural Science Foundation of China (No. 81960751, 81660705) and Guangxi Young and Middle-aged Teachers’ Research Ability Improvement Project (No. 2020KY59009), Guangxi Zhuangyao Pharmaceutical Key Laboratory (No. GXZYZZ2019-1, GXZYZZ2020-07), Guangxi Natural Science Foundation Youth Project (No. 2020GXNSFBA297094), Guangxi University of Traditional Chinese Medicine School-level Project Youth Fund (No. 2020QN006)

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Zheng, Y., Wang, L., Wang, Jh. et al. Effect of Curcumol on NOD-Like Receptor Thermoprotein Domain 3 Inflammasomes in Liver Fibrosis of Mice. Chin. J. Integr. Med. 28, 992–999 (2022). https://doi.org/10.1007/s11655-021-3310-0

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  • DOI: https://doi.org/10.1007/s11655-021-3310-0

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